Prebiotics provide fertile ground for growth

A quarter of a century ago, British researchers reported on a discovery that is now considered dogma: certain carbohydrates that are part of the diet can promote the (nonselective) growth of gut bacteria and thereby influence gut function.1

A large body of evidence has evolved since then, ushering in a category of natural bioactives called prebiotics, first introduced by name in 1995. Prebiotics are typically defined as nondigestible substrates that can be selectively fermented by the gut flora.2

Ingredients existing as or containing predominantly polymers (of varying length) of galactose and fructose, or galacto-oligosaccharides (GOS) and fructo-oligosaccharides (FOS)/inulin fructans, respectively, have received the keenest research focus. However, psyllium, rye flour, orange juice waste stream, wheat-derived resistant starch, gentiooligosaccharides, gum acacia, cereal-derived arabinoxylanoligosaccharides, and even carboxymethylcellulose have demonstrated or declared 'prebiotic' effects.3,4,5,6,7,8,9,10,11 Departing from the classical definition of prebiotic (as a fermentable substrate) is a low molecular-weight compound named 1,4-dihydroxy-2-naphthoic acid (DHNA), derived from the culture broth of a Propionobacterium species.12

The interest behind advocating the ingestion of a prebiotic is predicated upon the assumption that a measurable health outcome can be achieved — for example, reduction/prevention of diarrhoea or infection, rather than a surrogate marker like changes in the Bifidobacteria population in the gut/fecal flora. A small body of randomised, controlled clinical trials (RCT) in adults (paediatric studies excluded) has been conducted with prebiotics alone.

In one RCT with a maltodextrin placebo, 8g twice daily of oligofructose for eight weeks to seven subjects with nonalcoholic steatohepatitis (a noninfectious, chronic, enlarged-liver condition) produced a significant improvement in only one marker of liver function and no change in liver size.13

Systematic assessment of the effects upon a larger spectrum of the gut flora is needed
An RCT with 450 elderly hospitalised patients given broad-spectrum antibiotics assessed the effects of oligofructose (12g/day) or placebo. 14 The treatments were given through the antibiotic regimen, for seven days thereafter, and then for seven more days. Despite the oligofructose group showing an increase in fecal Bifidobacteria counts, the primary outcome measure of incidence of antibiotic-associated diarrhoea was not different from placebo.

Open-label studies have found benefits with prebiotics. In a study with 10 active Crohn's disease patients, a single daily 15g dose of FOS (Prebio 1, Nestlé, Switzerland; 70 per cent oligofructose and 30 per cent inulin) for three weeks produced a significant improvement in disease scores, faecal Bifidobacteria count and gut immunological parameters.15

Supplementation with 30g/day (10g, thrice daily) of germinated barley, a waste product from the brewing industry, augmented Bifidobacteria counts and improved disease symptoms in ulcerative colitis patients, accompanied by mild bloating.16

There is a definitive need for additional long-term RCTs in different populations, and for head-to-head comparisons of different prebiotics before they can be advocated unequivocally.17 Also, systematic assessment of the effects upon a larger spectrum of the gut flora is warranted, given the possibility of potentially undesirable flora inhabitants also being promoted.18

1. Stephen AM, Cummings JH. Mechanism of action of dietary fibre in the human colon. Nature 1980;284:283-4.
2. Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota. Introducing the concept of prebiotics. J Nutr 1995;125:1401-12.
3. Garcia-Cantu DA, et al. Utility of synbiotic therapy in acute pancreatitis. Gastroenterology 2005; 128(4, Suppl.2):A173.
4. Hongisto S-M, et al. A combination of fibre-rich rye bread and yoghurt containing Lactobacillus GG improves bowel function in women with self-reported constipation. Eur J Clin Nutr 2006;60:319-24.
5. Manderson K, et al. In vitro determination of prebiotic properties of oligosaccharides derived from an orange juice manufacturing by-product stream. Appl Environ Microbiol 2005;71:8383-89.
6. Pasman W, et al. Long-term gastrointestinal tolerance of NUTRIOSE? FB in healthy men. Eur J Clin Nutr doi:10.1038/sj.ejcn.1602418.
7. Sanz ML, et al. Selective fermentation of gentiobiose-derived oligosaccharides by human gut bacteria and influence of molecular weight. FEMS Microbiol Ecol doi:10.1111/j.1574-6941.2006.00075.
8. Dutcosky SM, et al. Combined sensory optimization of a prebiotic cereal product using multicomponent mixture. Food Chem 2006;98:630-8.
9. Snart J, et al. Supplementation of the diet with high-viscosity beta-glucan results in enrichment for lactobacilli in the rat cecum. Appl Environ Microbiol 2006;72:1925-31.
10. Bowen-Yacyshyn, MB, et al. Carboxy-methylcellulose (CMC) alters intestinal permeability, decreases inflammation and increases CEACAM1 isoform expression. Gastroenterology 2005;128(4,Suppl.2):A280.
11. Cloetens L, et al. Dose-response effect of arabinoxylanoligosacharides on the colonic NH3-metabolism using lactose-(15N, 15N')-ureide in healthy volunteers. Presented: Digestive Disease Week, Los Angeles, CA, 2006 May 24.
12. Okada Y, et al. Propionibacterium freudenreichii component 1.4-dihydroxy-2-naphthoic acid (DHNA) attenuates dextran sodium sulphate induced colitis by modulation of bacterial flora and lymphocyte homing. Gut 2006;55:681-8.
13. Daubiol CA, et al. Effects of oligofructose on glucose and lipid metabolism in nonalcoholic steatohepatitis. Eur J Clin Nutr 2005;59:723-6.
14. Lewis S, et al. Failure of dietary oligofructose to prevent antibiotic-associated diarrhoea. Aliment Pharmacol Ther 2005;21:469-77.
15. Lindsay JO, et al. Clinical, microbiological, and immunological effects of fructo-oligosaccharide in Crohn's disease. Gut 2006;55:348-55.
16. Kanauchi O, et al. Germinated barley foodstuff feeding a novel nutraceutical therapeutic strategy for ulcerative colitis. Digestion 2001;63:60-7.
17. De Preter V, et al. Differential effect of long-term dietary intake of lactulose and oligofructose-enriched inulin on the NH3-metabolism and predominant microbiota in the colon of healthy volunteers. Presented at Digestive Disease Week, Los Angeles, California, 2006 May 24.
18. Apajalahti JH, et al. Culture-independent microbial community analysis reveals that inulin in the diet primarily affects previously unknown bacteria in the mouse cecum. Appl Environ Microbiol 2002;68:4986-95.

Anthony Almada, MSc, is president and CSO of IMAGINutrition. Respond: [email protected]

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